The physiological role of AT1 receptors in the ventrolateral medulla

Abstract

Neurons in the rostral and caudal parts of the ventrolateral medulla (VLM) play a pivotal role in the regulation of sympathetic vasomotor activity and blood pressure. Studies in several species, including humans, have shown that these regions contain a high density of AT 1 receptors specifically associated with neurons that regulate the sympathetic vasomotor outflow, or the secretion of vasopressin from the hypothalamus. It is well established that specific activation of AT 1 receptors by application of exogenous angiotensin II in the rostral and caudal VLM excites sympathoexcitatory and sympathoinhibitory neurons, respectively, but the physiological role of these receptors in the normal synaptic regulation of VLM neurons is not known. In this paper we review studies which have defined the effects of specific activation or blockade of these receptors on cardiovascular function, and discuss what these findings tell us with regard to the physiological role of AT 1 receptors in the VLM in the tonic and phasic regulation of sympathetic vasomotor activity and blood pressure.

Evidence for a functional cardiac interaction between losartan and angiotensin‐(1–7) receptors revealed by orthostatic tilting test in rats

“…In this regard, it is known that losartan can cross the blood-brain barrier (Li et al, 1993;Polidori et al, 1996) or act at the area postrema, a circumventricular organ lacking a blood-brain barrier (Johnson & Gross, 1993). Also, losartan may act the rostral ventrolateral medulla, a key region involved in the tonic and reflex control of the sympathetic output (Tagawa et al, 2000) and where a high density of angiotensin receptors is present (Song et al, 1992). We are currently investigating this possibility.…”

Pregnancy increases baroreflex-independent GABAergic inhibition of the RVLM in rats

“…In regard to pregnancy, there is indirect evidence that sympathoexcitatory effects of angiotensin may be augmented (9,14,35,55). In addition, an interaction between GABA and ANG II has been demonstrated within the RVLM (63,68) and in other brain regions associated with cardiovascular function (1a, 19, 45). Results of the present experiments indicate that prior blockade of AT 1 receptors in the RVLM attenuated bicuculline-induced increases in MAP and RSNA to a similar degree in pregnant and nonpregnant rats.…”

“…In addition, there is evidence for a nonexcitatory amino acid excitatory influence in the RVLM (67). Angiotensin II (ANG II)-type 1 (AT 1 ) receptors are present (36, 70), and most studies support an overall excitatory effect of ANG II in the RVLM (19,36,68).The major source of baseline inhibition of the RVLM is through GABAergic projections from the caudal ventrolateral medulla (CVLM) (60), although other GABAergic influences including GABA interneurons within the RVLM may also contribute (19,29). In regard to arterial baroreflex-mediated sympathoinhibition, baroreceptor afferent nerves project to and excite second order neurons in the nucleus tractus solitarius (NTS), which ultimately results in inhibition of presympathetic neurons in the RVLM through an obligatory synapse in the CVLM and release of GABA in the RVLM (29,60).…”

“…In addition, there is evidence for a nonexcitatory amino acid excitatory influence in the RVLM (67). Angiotensin II (ANG II)-type 1 (AT 1 ) receptors are present (36, 70), and most studies support an overall excitatory effect of ANG II in the RVLM (19,36,68).…”

“…The present experiments were performed to test the hypothesis that the influence of arterial baroreflex-independent GABAergic inhibition of the RVLM is greater in near-term pregnant compared with nonpregnant rats. In addition, since an interaction has been shown between ANG II and GABA in the RVLM (63,68) and pregnancy is associated with a generalized upregulation of the renin-angiotensin system (47), the potential contribution of AT 1 receptor activation in the RVLM to differences between pregnant and nonpregnant rats was evaluated.…”